Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.27.1 (RNase)
 16,360 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The brain biochemistry in terms of certain key substances of brain were studied in 18% protein and 6% protein-fed rats following lead ingestion at a level of 1% in the diet. Lead ingestion diminished the protein and increased the RNA content of brain, and, consequently reduced the protein/RNA ratio. The RNA/DNA ratio in brain was elevated in lead toxicity, while the protein/DNA ratio remained unaltered. The RNase and DNase activities of brain were decreased. Lead treatment diminished the glutathione (GSH) level of blood but the GSH level of brain was not altered significantly by the lead treatment. The plasma protein level was also diminished after lead treatment. The effects of lead on some of these parameters were found to be more pronounced in rats receiving the 6% protein diet. The serotonin (5-HT) level of brain was reduced, while the norepinephrine (NE) and dopamine (DA) levels of brain were elevated following lead treatment. The monoamine oxidase (MAO) and tryptophan hydroxylase (TPH) activities and 5-hydroxy-indole acetic acid (5-HIAA) content of brain were elevated in lead-ingested rats. The effects of lead on these parameters were found to be potentiated when the rats were fed on a 6% protein diet. These studies suggest that lead at the present dose affects brain biochemistry in terms of both nucleic acids and amine metabolism, and protein deficiency potentiates some of these lead-induced changes.
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PMID:Impact of lead toxicity on brain metabolisms of nucleic acid and catecholamine in protein malnourished rats. 129 4

We have examined the expression of mRNAs encoding five major neurotransmitter-synthesizing enzymes in MAH cells, a clonal cell line derived by retroviral immortalization of a rat embryonic sympathoadrenal progenitor cell. These mRNAs include tyrosine hydroxylase (TH), choline acetyltransferase (ChAT), tryptophan hydroxylase (TpH), and glutamic acid decarboxylases (GADs) 1 and 2. We find that MAH cells express high levels of TH mRNA and low levels of ChAT and TpH mRNAs. Neither GAD1 nor GAD2 mRNAs are detectable using an RNase protection assay with a detection limit of less than one transcript per cell. A similar pattern of mRNA expression is observed in postnatal superior cervical ganglia, adrenal medulla, and in PC12 cells. Transmitter synthesis and accumulation assays indicate that MAH cells can synthesize both catecholamines and acetylcholine. Thus the TH and ChAT mRNAs detected in these cells are likely to be translated into active enzyme. To corroborate these data obtained using MAH cells, we performed similar transmitter synthesis and accumulation assays on sympathoadrenal progenitors directly isolated from E14.5 fetal adrenal glands by fluorescence-activated cell sorting. These progenitor cells also synthesize and accumulate both catecholamines and acetylcholine, albeit to different extents than MAH cells. Both MAH cells and their nonimmortal counterparts are able to increase slightly their cholinergic function upon short-term exposure to CDF/LIF, a factor known to induce acetylcholine synthesis in postmitotic sympathetic neurons. Taken together, these data suggest that progenitor cells in the sympathoadrenal lineage acquire the ability to simultaneously transcribe several different neurotransmitter enzyme genes early in development, prior to their choice of final cell fate. At the same time, the progenitors possess receptors which regulate expression of these genes in response to environmental factors. This ability may permit the cells to choose from several different transmitter phenotypes in response to different environments, as they migrate through the embryo. The persistent transcription of these genes in adult cells, moreover, may in part account for the phenotypic plasticity of cells in this lineage.
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PMID:Co-expression of multiple neurotransmitter enzyme genes in normal and immortalized sympathoadrenal progenitor cells. 168 90

Besides the classical endocrine renin-angiotensin system (RAS), a local RAS has been described also in the brain. We attempted to clarify the existence of a local RAS in the pineal gland. Through the use of a ribonuclease protection assay, it proved possible to detect the mRNA for angiotensinogen (AOGEN), for the angiotensin receptor type 1A (AT1a) and 1B (AT1b) and for the angiotensin-converting enzyme (ACE) in pineal glands from rats. Renin mRNA, however, could not be found by this method. By in situ hybridization and immunocytochemistry, AOGEN mRNA was co-localized with the astrocyte marker glial fibrillary acidic protein. AT1b mRNA expression exceeded the expression of AT1a mRNA and was co-localized with the pinealocyte-specific tryptophan hydroxylase. Thus, in the mammalian pineal gland there is a local formation of the components of the RAS. The presence of angiotensin II receptors further substantiates a role for angiotensins and the pineal RAS in the physiology of this gland.
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PMID:Local renin-angiotensin system in the pineal gland. 955 34

Tryptophan hydroxylase (TPH) is the rate limiting enzyme in serotonin biosynthesis [D.G. Grahame-Smith, Tryptophan hydroxylation in brain, Biochem. Biophys. Res. Commun. 16 (1964) 586-592 [19]]. As such, the TPH gene is a likely target for modulation of serotonergic function, which has been associated with several psychiatric disorders [E.C. Azmitia, P.M. Whitaker-Azmitia, Awakening the sleeping giant: anatomy and plasticity of the brain serotonergic system, J. Clin. Psychiatry 52 (12, Suppl.) (1991) 4-16 [1]; R.P. Hart, R. Yang, L.A. Riley., T.L. Green, Post-transcriptional control of tryptophan hydroxylase gene expression in rat brain stem and pineal gland, Mol. Cell. Neurosci. 2 (1991) 71-77 [20]; M.J. Owens, C.B. Numeroff, Role of serotonin in the pathophysiology of depression: focus on the serotonin transporter, Clin. Chem. 40 (1994) 288-295 [24]]. Unfortunately, it has been technically difficult to measure TPH mRNA levels in central serotonergic neurons due to its low levels. For example, detection with ribonuclease protection assays requires pooling of 5-10 dissected brainstems [M.C. Darmon, B. Guibert, V. Leviel, M. Ehret, M. Maitre, J. Mallet, Sequence of two mRNAs encoding active rat tryptophan hydroxylase, J. Neurochem. 51 (1988) 312-316 [15]; B.L. Jacobs, E.C. Azmitia, Structure and function of the brain serotonin system, Physiol. Rev. 72 (1992) 165-229 [21]]. This protocol describes the use of competitive RT-PCR to measure TPH mRNA levels from rat brain. First described in 1988, competitive RT-PCR has become an accepted method of measuring RNA abundance [M. Clementi, S. Menzo, P. Bagnarelli, A. Manzin, A. Valenza, P.E. Varaldo, Quantitative PCR and RT-PCR in virology, PCR Methods Appl. 2 (1994) 191-196 [12]; N.C.P. Cross, Quantitative PCR techniques and applications, Br. J. Haematol. 89 (1995) 693-697 [14]; K.P. Foley, M.W. Leonard, J.D. Engel, Quantitation of RNA using the polymerase chain reaction, Trends Genet. 9 (1993) 380-385 [17]; P.D. Siebert, J.W. Larrick, Competitive PCR, Nature 359 (1992) 558 [27]]. Competitive RT-PCR uses co-amplification with a known quantity of an in vitro transcribed RNA which amplifies using the same primers and thus competes for reactants with the product of interest. As the two products amplify with the same efficiency, the relative abundance of the two amplification products remains constant, and thus can be used to determine initial tissue TPH mRNA levels [G. Gilliland, S. Perrin, K. Blanchard, H.F. Bunn, Analysis of cytokine mRNA and DNA: detection and quantitation by competitive polymerase chain reaction, Proc. Natl. Acad. Sci. U.S.A. 87 (1990) 2725-2729 [18]; A.M. Wang, M. V. Doyle, D.F. Mark, Quantitation of mRNA by the polymerase chain reaction, Proc. Natl. Acad. Sci. U.S.A. 86 (1989) 9717-9721 [31]]. We first demonstrate equivalent results between RNA slot blots and competitive RT-PCR using the CA77 thyroid C cell line [M.S. Clark, A. F. Russo, Tissue-specific glucocorticoid regulation of tryptophan hydroxylase mRNA levels, Mol. Brain Res. 48 (1997) 346-354 [9]]. We then describe the use of competitive RT-PCR to measure TPH mRNA levels in RNA isolated from rat brain poly-A+ RNA.
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PMID:Measurement of tryptophan hydroxylase mRNA levels by competitive RT-PCR. 963 Jun 72

Serotonin (5-HT) is a monoaminergic neurotransmitter involved in various processes in the mammalian nervous system with tryptophan hydroxylase (TPH) as the rate-limiting enzyme in its biosynthesis. Interestingly, there is accumulating evidence that neurotransmitters including 5-HT are directly involved in cleavage divisions and morphogenetic movements during early embryogenesis, even before neurons appear. Clonal cell models will be indispensable for investigating these pre-neuronal actions of neurotransmitter systems. Totipotent embryonic stem (ES) cells represent early embryonic stages, are amenable to genetic manipulations and can be easily induced to differentiate into cells with neuronal and glial properties enabling the recapacitation of neurulation. In this study, we used high-pressure liquid chromatography with fluorometric detection (HPLC-FD) to demonstrate the presence of 5-HT in ES cells. In addition, RNase protection assays and immunohistochemical methods detected TPH mRNA and protein, respectively, confirming the endogeneous production of 5-HT in these cells. Furthermore, TPH protein was detected in mouse zygotes after fertilization. These results indicate that ES cells may be useful for the investigation of neurotransmitters in pre-nervous embryos and their actions during ontogeny.
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PMID:Serotonin synthesis in murine embryonic stem cells. 1032 Jul 83

We have cloned a segment of the rat tryptophan hydroxylase (TPH) gene and used it to investigate differences in mRNA levels in two tissues: brain stem and pineal gland. The cloned, 13-kb genomic region contains five exons corresponding to cloned TPH cDNA sequence. Most intron/axon junctions are homologous to those found in the closely related genes encoding tyrosine and phenylalanine hydroxylase. The gene segment contains a region of low complexity that is repeated in the genome, but the remainder of the segment is single-copy sequence. TPH mRNAs can be detected by RNase protection assays and demonstrate a large difference in steady-state mRNA levels between pineal gland and brain stem dissections, agreeing with the results of Dumas and collaborators (1989, J. Neurosci. Res. 24:537-547). However, nuclear run-on assays of TPH gene transcription rates reveal similar levels of gene expression for pineal and brain stem. Control of TPH mRNA levels, therefore, appears to be post-transcriptional.
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PMID:Post-transcriptional control of tryptophan hydroxylase gene expression in rat brain stem and pineal gland. 1991 85